We are actively studying the potential physiological role of oxidative modification of proteins. The current focus of this project concerns three areas, (1) neutrophil activation, (2) the role of protein kinase C in neutrophil activation, and (3) studies on a gliosis model system. Earlier studies have indicated that activated neutrophils can catalyze the oxidative modification of glutamine synthetase in intact E. coli as well the oxidative modification of endogenous neutrophil enzymes. These studies have shown that both the kinetics and the properties of the reaction are influenced by the activating agent (and/or the differentiating agent in the case of HL-60 cells). These results have suggested the presence of multiple pathways for neutrophil activation. In order to elucidate the fundamental differences in these pathways, we have studied some reactions which appear to be relatively specific for a pathway activated by PMA. We present here evidence that tyrosine is incorporated into proteins of activated neutrophils by a mechanism which is independent of protein synthesis but is dependent on PMA-stimulated respiratory burst activity. In other studies we are examining the role of protein kinase C in neutrophil activation. We have demonstrated that several proteins are phosphorylated in a protein kinase C-dependent reaction following PMA activation. Finally, we are studying the oxidative modification of proteins in a culture system which is used for model of gliosis.